Blood mononuclear cells (MNc) were isolated from healthy

volunteers. Results: HSCs exposed to M-tropic gp120 (CN54) showed a time-dependent up-regulation of Pycard, NALP3, Caspase-1 and IL-1 β. ELISA showed increased levels of mature IL-1 β in the supernatants of gp120-stimulated cell. Pre-incubation of HSC with neutralizing anti-CCR5 antibody reduced gp120-mediated IL-1 β production, showing that this receptor is required for activation of the inflammasome complex by gp120. Similar results were obtained in MNc, where a CCR5 receptor antagonist blocked inflammasome activation and IL-1 β production. gp120 was buy Adriamycin found to modulate the expression of different miRNAs, and in particular to down-regulate mir29b in HSC. Transfection of a miR-29b

mimic in HSC blocked the ability of gp120 to induce procollagen-1 expression, α-SMAand TGF-β, while didn’t affect IL-1b induction. Conclusions: These data indicate that at least two pathways mediate the effects of gp120 on monuclear cells and activated HSC. Inflammasome activation through engagement of CCR5 contributes X-396 molecular weight to proinflamatory actions, whereas down-regulation of miR-29b regulates expression of procollagen-1, alpha-SMA and TGF-β. Disclosures: Andrea Cappon – Grant/Research Support: ViiV Fabio Marra – Advisory Committees or Review Panels: Abbott; Consulting: Bayer Healthcare; Grant/Research Support: ViiV The following people have nothing to disclose: Raffaele Bruno, Sandra Gessani, Andrea Masotti Introduction: We have already shown an important role of TLR-dependent formed Thromboxane (TX) for portal hypertension in cirrhosis in previous work (including Steib CJ et al., Hepatology 2010). Aim of the present study was to determine, which liver cells play a relevant role for TX-production and which TLR are involved in this process. Methods: KC and SEC were isolated from mouse livers (male C57/Bl6) and stimulated Clomifene over 24h with various TLR-agonists (Pam3CSK4 [TLR 1/2] 0,1g/ml; HKLM [TLR 2] 10e8 cells/ml; Poly (I:C) [TLR 3] 10ng/ ml; LPS-EK [TLR

4] 10ng/ml; ST-FLA [TLR 5] 10ng/ml; FSL-1 [TLR 6/2] 1ng/ml; ssRNA40 [TLR 7] 0,25μg/ml; ODN1826 [TLR 9] 5liM; n=6 each). Thromboxane B2 (TXB2) efflux before and after stimulation into the cell media was measured by ELISA (mean±SD, *p<0.05). Results: TXB2-efflux (before stimulation vs. after stimulation in pg/ml) is shown in table 1. Conclusion: The activation of TLR 2, 4, 5, 2/6, and 9 on isolated KC of healthy livers lead to a significant production of vasoconstrictive effective TXB2, whereas the activation of SEC through TLR 1/2, 3, 4, 6, 7 and 9 led to a decrease of TXB2 production. Our findings provide an important basis to identify relevant early stage microbial products for the formation of TXB2 in the future and to develop targeted strategies to prevent complications of portal hypertension. *p<0.05 Disclosures: The following people have nothing to disclose: Julia Schewe, Lisa Selzner, Ingrid Liss, Burkhard Goke, Alexander L. Gerbes, Christian J.